Influence of selective fluorination on the biological activity and proteolytic stability of glucagon-like peptide-1.
The relative simplicity and high specificity of peptide therapeutics has fueled recent interest. However, peptide and protein drugs generally require injection and suffer from low metabolic stability. We report here the design, synthesis, and characterization of fluorinated analogues of the gut hormone peptide, GLP-1. Overall, fluorinated GLP-1 analogues displayed higher proteolytic stability with simultaneous retention of biological activity (efficacy). Fluorinated amino acids are useful for engineering peptide drug candidates and probing ligand-receptor interactions.
Meng
He
H
Department of Chemistry, Tufts University, Medford, Massachusetts 02155, USA.
Krishnaji
Subrahmanian Tarakkad
ST
Beinborn
Martin
M
Kumar
Krishna
K
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002522:Chlorocebus aethiops; D015195:Drug Design; D052216:Glucagon-Like Peptide 1 / Q000138:chemical synthesis / Q000737:chemistry*; D054879:Halogenation; D007930:Leucine / Q000031:analogs & derivatives* / Q000737:chemistry; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D055550:Protein Stability
C445784:hexafluoroleucine; D052216:Glucagon-Like Peptide 1; D007930:Leucine